Letter to the Editor: The mucosal gut signature in primary sclerosing cholangitis before and after liver transplantation. Is the dysbiosis index really predictive for the recurrence of PSC?
Authors: Ruslan A. Mammadov, Thijmen Visseren, Henk P. Roest, Luc J.W. van der Laan, Maikel P. Peppelenbosch
Journal: Hepatology (2023)

To the editor, We read with great interest the study by Hole and coauthors,1 reporting on the changes in the microbiota in patients with PSC. The authors show consistent mucosal microbiota features associated with PSC disease severity apparently independent of liver transplantation status, and reported that the dysbiosis index values correlate with recurrent disease and reduced graft survival. They suggest that the impact of gut microbiota on post-transplant liver health should be investigated further. We feel, however, that this conclusion understates the importance of pretransplant mucosal microbiome composition in disease progression. In a previous study, we compared the ileocolonic mucosal pretransplant microbiome in a series of 98 PSC patients with or without recurrence.2 A striking result was that the increased presence of the Gammaproteobacteria Shigella in the pretransplant microbiome was associated with protection against the recurrence of PSC following liver transplantation. After re-evaluating the microbiome data of our cohort, prompted by the study by Hole and colleagues, we observed that Fusobacteriaceae and Moraxellaceae showed lower abundance in the recurrence group (Figure 1A, B). This protective effect of Fusobacteriaceae and Moraxellaceae is present in PSC patients with and without concurrent inflammatory bowel disease (Figure 1C, D).FIGURE 1: Detection of Fusobacteriaceae (A) and Moraxellaceae (B) in patients with rPSC, and without recurrence of PSC after liver transplantation (Chi-square test). Detection of Fusobacteriaceae (C) and Moraxellaceae (D) in patients with (UC or CD) and without (no IBD) inflammatory bowel disease (IBD) (Chi-square test). Abbreviations: CD, Crohn disease; IBD, inflammatory bowel disease; PSC, primary sclerosing cholangitis; rPSC, recurrence of PSC; UC, ulcerative colitis.This observation is broadly in line with that of Hole and colleagues in that composition of pretransplant mucosal microbiome aligns with PSC clinical properties, but also shows that dysbiosis per se is not necessarily associated with clinical outcome, at least with respect to PSC recurrence, as our data suggest. We did not find any correlation between the dysbiotic effect of Moraxellaceae and Fusobacteriaceae, neither with the Mayo PSC score nor the AOM PSC score (data not shown). Interestingly, Veillonellaceae, not dysbiotic in our cohort, had a correlation with the Mayo PSC score (r=1.21, p=0.039). In our opinion, the protective influence of Shigella, Fusobacteria, and Moraxella, generally considered pathogenic organisms, should be interpreted as individual bacterial groups and not solely as a component of the dysbiosis index. Furthermore, our previous study highlights the importance of the pretransplant microbiome for PSC post-transplant outcome. Although the post-transplant microbiome is certainly an important and still-understudied factor, this should not distract scientists from further investigations into the mechanisms mediating the effects of bacterial species present in the pretransplant mucosa as well. Interpreting our results in conjunction with those now obtained by Hole and colleagues, the interesting possibility emerges that mucosal microbiome sampling may come to replace more invasive sampling (liver biopsy) in the clinical management of PSC, especially when microbiome determinations are compared with other biomarkers and genetic data.